Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-rel...Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties.Despite its widespread use,scientific evidence validating the antifungal efficacy of A.argyi water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains limited.This study aimed to substantiate the scientific basis of the folkloric use of A.argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes.The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species.The subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent subfraction.The minimum inhibitory concentrations(MICs)of AAWE6 against T.rubrum,M.gypseum,and T.mentagrophytes were 312.5,312.5,and 625μg·mL−1,respectively.Transmission electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T.rubrum,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy metabolism.Additionally,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of AAWE6.In conclusion,the subfraction AAWE6 from A.argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function.This research validates the traditional use of A.argyi and provides scientific support for its antidermatophytic applications,as recognized in the Chinese patent(No.ZL202111161301.9).展开更多
Objective： To investigate the neuro-protective effects of Acanthopanax senticosus Harms（EAS） on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson＇s disease（PD）. Methods： T...Objective： To investigate the neuro-protective effects of Acanthopanax senticosus Harms（EAS） on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson＇s disease（PD）. Methods： The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms（EAS） was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP（MPTP＋EAS group, 10 in each group）. The MPTP model group and the MPTP＋EAS group received MPTP-HCl（30 mg/kg i.p） once a day for 5 days. The control group received an equal volume of saline（20 m L/kg i.p） once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily（MPTP-HCl, 30 mg/kg） for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2（NDUFV2）, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1（MT-ND1）, succinate dehydrogenase complex subunit A（SDHA）, and succinate dehydrogenase cytochrome b560 subunit（SDHC）. Results： After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly（P〈0.05）. EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential（both P〈0.05）, which was supported by an ultra-structural level analysis. The changes in reactive oxygen species（ROS）, malonic dialdehyde（MDA）, oxidative phosphorylation（OXPHOS） system 4 subunits levels and PD-related proteins expressions（parkin, Pink1, DJ-1, α-synuclein, and Lrrk2） reverted to near normal levels（all P〈0.05）, based on the results of immune-histological and Western blotting observations. Conclusions： The neuro-protective effects of EAS are linked to protecting mice against MPTPinduced mitochondrial dysfunction and structuraldamage.Therefore,EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders,such as PD.展开更多
Objective To investigate the role of a potential diabetes related mitochondrial region, which includes two previously reported mutations, 3243AG and 3316GA, in Chinese patients with adult onset type 2 diabetes Met...Objective To investigate the role of a potential diabetes related mitochondrial region, which includes two previously reported mutations, 3243AG and 3316GA, in Chinese patients with adult onset type 2 diabetes Methods A total of 277 patients and 241 normal subjects were recruited for the study Mitochondrial nt 3116-3353, which spans the 16S rRNA, tRNA leu(UUR) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR restriction fragment length polymorphism and allele specific PCR Variants were analyzed by two tailed Fisher exact test The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3 Results Four homoplasmic nucleotide substitutions were observed, 3200TC, 3206CT, 3290TC and 3316GA Only the 3200TC mutation is present in the diabetic population and absent in the control population No statistically significant associations were found between the other three variants and type 2 diabetes The 3200TC and 3206CT nucleotide substitutions located in 16S rRNA are novel variants The 3200TC caused a great alteration in the minimal free energy secondary structure model while the 3206CT altered normal 16S rRNA structure little Conclusions The results suggest that the 3200TC mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral In contrast to the Japanese studies, the 3316GA does not appear to be related to type 2 diabetes展开更多
Common wheat （Triticum aestivum L.） is one of the most important crops, and intra-specific wheat hybrids have obvious heterosis in yield and protein quality. Therefore, utilization of hybrid wheat varieties offers a...Common wheat （Triticum aestivum L.） is one of the most important crops, and intra-specific wheat hybrids have obvious heterosis in yield and protein quality. Therefore, utilization of hybrid wheat varieties offers an effective way to increase yield and nutrition. Cytoplasmic male sterility （CMS） systems are a useful genetic tool for hybrid crop breeding, and are ideal models for studying the genetic interaction and cooperative function of mitochondrial and nuclear genomes in plants （Schnable and Wise, 1998; Hanson and Bentolila, 2004）.展开更多
Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular recesses.However,the genetic etiology of 40%–60%of NVM cases remai...Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular recesses.However,the genetic etiology of 40%–60%of NVM cases remains unknown.Here,we identify two infants with NVM,in a nonconsanguineous family,with a typical clinical presentation of persistent bradycardia since the prenatal period.A homozygous missense variant(R223L)of RCAN family member 3(RCAN3)is detected in both infants using whole-exome sequencing.In the zebrafish model,marked cardiac dysfunction is detected in rcan3 deficiency(MO-rcan3^(ATG)-injected)and rcan^(−/−) embryos.Developmental dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient embryos.RCAN3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout;however,hRCAN3 mRNAs rescue these phenotypes.RNA-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish model.In human cardiomyocytes,RCAN3 deficiency results in reduced proliferation and increased apoptosis,together with an abnormal mitochondrial ultrastructure.Thus,we suggest that RCAN3 is a susceptibility gene for cardiomyopathies,especially NVM and that the R223L mutation is a potential loss-of-function variant.展开更多
In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cogn...In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM_（2.5） inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice. Furthermore, excessive reactive oxygen species generation was involved in the impairment. Interestingly, these alterations were partially reversed after exposure to PM_（2.5） ended. These findings clarify the mechanism involved in mitochondrial abnormality-related neuropathological dysfunction in response to atmospheric PM_（2.5） inhalation and provide an optimistic sight for alleviating the adverse health outcomes in polluted areas.展开更多
This study investigated the antifungal activity and possible mode of action of Bacillus pumilus HN-10 antifungal peptide P-1 against Trichothecium roseum.The results showed that the antifungal peptide P-1 at a concent...This study investigated the antifungal activity and possible mode of action of Bacillus pumilus HN-10 antifungal peptide P-1 against Trichothecium roseum.The results showed that the antifungal peptide P-1 at a concentration of 1.0μg mL^(-1)had strong antifungal activity against T.roseum.P-1 inhibited the tricarboxylic acid cycle(TCA)pathway and the transporter pathway of NADH to coenzyme Q on the electron transport chain.P-1 significantly reduced succinate dehydrogenase(SDH),malate dehydrogenase(MDH),ATPase,mitochondrial complex enzymes I,II and IV enzyme activities on the electron transport chain,and 5'-triphosphate(ATP),5'-diphosphate(ADP),5'-monophosphate(AMP)content,and energy charge(EC);significantly increased 6-phosphofructokinase(PFK)enzyme activity.The release of Ca^(2+)(OD_(680))from the inner mitochondrial membrane and the openness of the mitochondrial permeability transition pore(MPTP)were analysed,and microscopy was performed following staining of mitochondria with JC-1.The results indicated that P-1 significantly increased the release of Ca^(2+) and the openness of MPTP,decreased the mitochondrial membrane potential,and produced green fluorescence;transcriptomics data analysis showed that there were 39 differentially expressed genes(DEGs)related to energy metabolism enzymes.The results verified by qRT-PCR were basically consistent with the transcriptome sequencing results.Thus,P-1 achieved its inhibitory effect mainly by regulating genes related to energy metabolism.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.32270391)the Natural Science Foundation of Hubei Province(Nos.2023AFA032 and 2022CFB391)+1 种基金the Young Qihuang Scholars of the State Administration of Traditional Chinese Medicine,Hubei Province Administration of Traditional Chinese Medicine Research Project(No.ZY2023Z023)the Earmarked Fund for CARS-21 and Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(No.2060302).
文摘Artemisia argyi(A.argyi),a plant with a longstanding history as a raw material for traditional medicine and functional diets in Asia,has been used traditionally to bathe and soak feet for its disinfectant and itch-relieving properties.Despite its widespread use,scientific evidence validating the antifungal efficacy of A.argyi water extract(AAWE)against dermatophytes,particularly Trichophyton rubrum,Trichophyton mentagrophytes,and Microsporum gypseum,remains limited.This study aimed to substantiate the scientific basis of the folkloric use of A.argyi by evaluating the antifungal effects and the underlying molecular mechanisms of its active subfraction against dermatophytes.The results indicated that AAWE exhibited excellent antifungal effects against the three aforementioned dermatophyte species.The subfraction AAWE6,isolated using D101 macroporous resin,emerged as the most potent subfraction.The minimum inhibitory concentrations(MICs)of AAWE6 against T.rubrum,M.gypseum,and T.mentagrophytes were 312.5,312.5,and 625μg·mL−1,respectively.Transmission electron microscopy(TEM)results and assays of enzymes linked to cell wall integrity and cell membrane function indicated that AAWE6 could penetrate the external protective barrier of T.rubrum,creating breaches(“small holes”),and disrupt the internal mitochondrial structure(“granary”).Furthermore,transcriptome data,quantitative real-time PCR(RT-qPCR),and biochemical assays corroborated the severe disruption of mitochondrial function,evidenced by inhibited tricarboxylic acid(TCA)cycle and energy metabolism.Additionally,chemical characterization and molecular docking analyses identified flavonoids,primarily eupatilin(131.16±4.52 mg·g^(−1))and jaceosidin(4.17±0.18 mg·g^(−1)),as the active components of AAWE6.In conclusion,the subfraction AAWE6 from A.argyi exerts antifungal effects against dermatophytes by disrupting mitochondrial morphology and function.This research validates the traditional use of A.argyi and provides scientific support for its antidermatophytic applications,as recognized in the Chinese patent(No.ZL202111161301.9).
基金Supported by the National Natural Science Foundation of China(No.81270056)China Postdoctoral Science Foundation(No.2013T60398)+2 种基金Scientific Research grants of Postdoctoral Researchers Settled in Heilongjiang(No.LBH-Q13160)Outstanding Talents Cultivation Fund of Heilongjiang University of Chinese Medicine(No.2013jc01)the Outstanding Innovative Talent Support Programs of Heilongjiang University of Chinese Medicine
文摘Objective： To investigate the neuro-protective effects of Acanthopanax senticosus Harms（EAS） on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson＇s disease（PD）. Methods： The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms（EAS） was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP（MPTP＋EAS group, 10 in each group）. The MPTP model group and the MPTP＋EAS group received MPTP-HCl（30 mg/kg i.p） once a day for 5 days. The control group received an equal volume of saline（20 m L/kg i.p） once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily（MPTP-HCl, 30 mg/kg） for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2（NDUFV2）, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1（MT-ND1）, succinate dehydrogenase complex subunit A（SDHA）, and succinate dehydrogenase cytochrome b560 subunit（SDHC）. Results： After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly（P〈0.05）. EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential（both P〈0.05）, which was supported by an ultra-structural level analysis. The changes in reactive oxygen species（ROS）, malonic dialdehyde（MDA）, oxidative phosphorylation（OXPHOS） system 4 subunits levels and PD-related proteins expressions（parkin, Pink1, DJ-1, α-synuclein, and Lrrk2） reverted to near normal levels（all P〈0.05）, based on the results of immune-histological and Western blotting observations. Conclusions： The neuro-protective effects of EAS are linked to protecting mice against MPTPinduced mitochondrial dysfunction and structuraldamage.Therefore,EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders,such as PD.
文摘Objective To investigate the role of a potential diabetes related mitochondrial region, which includes two previously reported mutations, 3243AG and 3316GA, in Chinese patients with adult onset type 2 diabetes Methods A total of 277 patients and 241 normal subjects were recruited for the study Mitochondrial nt 3116-3353, which spans the 16S rRNA, tRNA leu(UUR) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR restriction fragment length polymorphism and allele specific PCR Variants were analyzed by two tailed Fisher exact test The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3 Results Four homoplasmic nucleotide substitutions were observed, 3200TC, 3206CT, 3290TC and 3316GA Only the 3200TC mutation is present in the diabetic population and absent in the control population No statistically significant associations were found between the other three variants and type 2 diabetes The 3200TC and 3206CT nucleotide substitutions located in 16S rRNA are novel variants The 3200TC caused a great alteration in the minimal free energy secondary structure model while the 3206CT altered normal 16S rRNA structure little Conclusions The results suggest that the 3200TC mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral In contrast to the Japanese studies, the 3316GA does not appear to be related to type 2 diabetes
基金supported by the National Natural Science Foundation of China(No.30971844)the Fundamental Research Funds of Northwest A & F University(No. QN2011003)+1 种基金China Postdoctoral Science Foundation to Wang Junwei(No.20070410835)the Tang Zhong-Ying Breeding Funding Project of Northwest A & F University
文摘Common wheat （Triticum aestivum L.） is one of the most important crops, and intra-specific wheat hybrids have obvious heterosis in yield and protein quality. Therefore, utilization of hybrid wheat varieties offers an effective way to increase yield and nutrition. Cytoplasmic male sterility （CMS） systems are a useful genetic tool for hybrid crop breeding, and are ideal models for studying the genetic interaction and cooperative function of mitochondrial and nuclear genomes in plants （Schnable and Wise, 1998; Hanson and Bentolila, 2004）.
基金the National Key Research and Development Program of China(2022YFC2703302)the National Natural Science Foundation of China(82271692)+3 种基金the Sichuan Province Science and Technology Support Program,China(2022YFS0078)the Natural Science Foundation of Sichuan Province(2022NSFSC0782)the Fundamental Research Funds for the Central Universities(SCU2022F4080)Horizontal research project of Sichuan University(21H1095 and 21H1116).
文摘Noncompaction of the ventricular myocardium(NVM),the third most diagnosed cardiomyopathy,is characterized by prominent trabeculae and intratrabecular recesses.However,the genetic etiology of 40%–60%of NVM cases remains unknown.Here,we identify two infants with NVM,in a nonconsanguineous family,with a typical clinical presentation of persistent bradycardia since the prenatal period.A homozygous missense variant(R223L)of RCAN family member 3(RCAN3)is detected in both infants using whole-exome sequencing.In the zebrafish model,marked cardiac dysfunction is detected in rcan3 deficiency(MO-rcan3^(ATG)-injected)and rcan^(−/−) embryos.Developmental dysplasia of both endocardial and myocardial layers is also detected in rcan3-deficient embryos.RCAN3 R223L variant mRNAs can not rescue heart defects caused by rcan3 knockdown or knockout;however,hRCAN3 mRNAs rescue these phenotypes.RNA-seq experiments show that several genes involved in cardiomyopathies are significantly regulated through multiple signaling pathways in the rcan3-knockdown zebrafish model.In human cardiomyocytes,RCAN3 deficiency results in reduced proliferation and increased apoptosis,together with an abnormal mitochondrial ultrastructure.Thus,we suggest that RCAN3 is a susceptibility gene for cardiomyopathies,especially NVM and that the R223L mutation is a potential loss-of-function variant.
基金supported by the National Science Foundation of China(Nos.21377076,91543203,21477070,21222701)Specialized Research Fund for the Doctoral Program of Higher Education of China(Nos.20121401110003,20131401110005)+1 种基金Project Supported by Shanxi Young Sanjin Scholarship of China,Program for the Outstanding Innovative Teams of Higher Learning Institutions of ShanxiResearch Project Supported by Shanxi Scholarship Council of China(No.2015-006)
文摘In light of the accelerated aging of the global population and the deterioration of the atmosphere pollution, we sought to clarify the potential mechanisms by which fine particulate matter（PM_（2.5）） can cause cognitive impairment and neurodegeneration through the alteration of mitochondrial structure and function. The results indicate that PM_（2.5） inhalation reduces ATP production by disrupting the aerobic tricarboxylic acid cycle and oxidative phosphorylation, thereby causing the hypophosphorylation of tau in the cortices of middle-aged mice. Furthermore, excessive reactive oxygen species generation was involved in the impairment. Interestingly, these alterations were partially reversed after exposure to PM_（2.5） ended. These findings clarify the mechanism involved in mitochondrial abnormality-related neuropathological dysfunction in response to atmospheric PM_（2.5） inhalation and provide an optimistic sight for alleviating the adverse health outcomes in polluted areas.
基金financially supported by National Key R&D Program of China(2018YFD0400205).
文摘This study investigated the antifungal activity and possible mode of action of Bacillus pumilus HN-10 antifungal peptide P-1 against Trichothecium roseum.The results showed that the antifungal peptide P-1 at a concentration of 1.0μg mL^(-1)had strong antifungal activity against T.roseum.P-1 inhibited the tricarboxylic acid cycle(TCA)pathway and the transporter pathway of NADH to coenzyme Q on the electron transport chain.P-1 significantly reduced succinate dehydrogenase(SDH),malate dehydrogenase(MDH),ATPase,mitochondrial complex enzymes I,II and IV enzyme activities on the electron transport chain,and 5'-triphosphate(ATP),5'-diphosphate(ADP),5'-monophosphate(AMP)content,and energy charge(EC);significantly increased 6-phosphofructokinase(PFK)enzyme activity.The release of Ca^(2+)(OD_(680))from the inner mitochondrial membrane and the openness of the mitochondrial permeability transition pore(MPTP)were analysed,and microscopy was performed following staining of mitochondria with JC-1.The results indicated that P-1 significantly increased the release of Ca^(2+) and the openness of MPTP,decreased the mitochondrial membrane potential,and produced green fluorescence;transcriptomics data analysis showed that there were 39 differentially expressed genes(DEGs)related to energy metabolism enzymes.The results verified by qRT-PCR were basically consistent with the transcriptome sequencing results.Thus,P-1 achieved its inhibitory effect mainly by regulating genes related to energy metabolism.
